颈动脉球囊损伤大鼠白细胞介素6、白细胞介素10及白细胞介素17A mRNA表达：罗格列酮干预的意义

Effects of rosiglitazone on the mRNA expression of interleukin-6,interleukin-10 and interleukin-17A in rats after carotid artery balloon injury

背景:炎症在球囊损伤后血管增生中起重要作用,抑制炎症的发生、发展可以减少血管成形后再狭窄。研究表明PPARγ激动剂对抑制炎症发生有一定作用。目的:观察大鼠颈动脉损伤后炎症因子的变化及应用PPARγ激动剂罗格列酮干预后的表达变化。设计、时间及地点:随机对照动物实验,于2009-01/06在深圳市人民医院中心实验室完成。材料:SPF级雄性SD大鼠,体质量350g左右,用于制备颈动脉球囊导管损伤模型。方法:36只SD大鼠随机数字表法分为3组,每组12只。对照组:生理盐水灌胃4d后行假手术,术后13d予生理盐水灌胃;球囊损伤组:生理盐水灌胃4d后行左侧颈总动脉行球囊损伤,术后予生理盐水灌胃13d;罗格列酮组:罗格列酮灌胃4d后行左侧颈总动脉球囊损伤,术后罗格列酮灌胃13d。主要观察指标:术后14d麻醉处死并取左侧颈总动脉,损伤血管行苏木精-伊红染色,观察内膜变化。Real time RT-PCR检测大鼠损伤血管组织中白细胞介素6、白细胞介素10、白细胞介素17A mRNA水平。Western Blot检测大鼠损伤血管组织中核因子κB水平。结果:36只大鼠因造模失败和死亡排除5只,进入结果分析31只。①罗格列酮组白细胞介素6、白细胞介素17A mRNA表达水平明显低于球囊损伤组但高于对照组(P<0.05)。罗格列酮组白细胞介素10 mRNA表达高于球囊损伤组和对照组(P<0.05)。②罗格列酮组核因子κB水平明显低于球囊损伤组但高于对照组(P<0.05)。③球囊损伤后,内膜面积增厚,内膜/中膜比率增长,与对照组相比,差异有显著性意义(P<0.05)。罗格列酮治疗后内膜面积及内膜面积/中膜面积较球囊损伤减小但高于对照组(P<0.05)。结论:罗格列酮通过核因子κB调节白细胞介素6、白细胞介素10、白细胞介素17A mRNA表达,调节炎症因子的平衡,抑制损伤血管的炎症反应,减轻损伤血管的狭窄。

BACKGROUND： Inflammation plays an important role in vessel proliferation after balloon injury. Reducing inflammatory reaction may lighten the ocurrence and development of the restenosis after angioplasty. Studies have demonstrated that PPARy excitomotor has inhibitory effects on inflammation development. OBJECTIVE; To observe the changes in inflammatory factors after carotid artery balloon injury in rats and the intervention of PPARy excitomotor rosiglitazone. DESIGN, TIME AND SETTING： The randomized, controlled animal experiment was performed at the Central Laboratory of Shenzhen People＇s Hospital from January to June 2009. MATERIALS： Male SPF SD rats weighing about 350 g were selected to generate models of carotid balloon injury. METHODS： SD rats were equally and randomly divided into 3 groups： the control group, the balloon injury group and the rosiglitazone group. The left common carotid arteries were injured by balloon in the balloon injury group and the rosiglitazone group. The control group received sham operation. The rosiglitazone group was administered rosiglitazone daily by gavage,which began 4 days before operation and continued until harvesting.Accordingly,the control group and the balloon injury group were administered normal saline daily by gavage. MAIN OUTCOME MEASURES： All rats were executed under anesthesia at 14 days after operation, respectively to harvest left common carotid artery samples. The vessels were stained by hematoxylin-eosin, and Neointimal area （NIA） and media area （MA） as well as NIA/MA were calculated. Real time RT-PCR and Western Blot method were used to assay the expression of interleukin （IL）-6, IL-10, IL-17A mRNA and the distribution of nuclear factor （NF）-KB protein. RESULTS; Of the 36 rats, 5 were excluded due to failed modeling or death,and 31 rats were included in final analysis.①The expression levels of IL-6 and IL-17A mRNA in the rosiglitazone group were significantly lower than the balloon injury group, but higher than the control group（ P 〈 0.05）. The expression levels of IL-10 mRNA in the rosiglitazone group were higher than the balloon injury group and the control group （P〈 0.05）.②The expression levels of NF-KB in the rosiglitazone group were significantly lower than the balloon injury group, but higher than the control group （P 〈 0.05）.③NIA and MA as well as NIA/MA in the rosiglitazone group was clown-regulated, and lower than the balloon injury group, but higher than control group （P 〈 0.05）. CONCLUSION： Rosiglitazone can regulate the expression of 11-6 IL-10 IL-17A mRNA and the balance of inflammatory factors via NF-κB,inhibit the inflammatory reaction of injured vessels and may contribute to lighten the restenosis of injured vessels.